通过敲入细胞周期蛋白E挽救细胞周期蛋白D1缺陷。
Rescue of cyclin D1 deficiency by knockin cyclin E.
作者信息
Geng Y, Whoriskey W, Park M Y, Bronson R T, Medema R H, Li T, Weinberg R A, Sicinski P
机构信息
Dana-Farber Cancer Institute, and Department of Pathology, Harvard Medical School, Boston, Massachusetts 02115, USA.
出版信息
Cell. 1999 Jun 11;97(6):767-77. doi: 10.1016/s0092-8674(00)80788-6.
D-type cyclins and cyclin E represent two very distinct classes of mammalian G1 cyclins. We have generated a mouse strain in which the coding sequences of the cyclin D1 gene (Ccnd1) have been deleted and replaced by those of human cyclin E (CCNE). In the tissues and cells of these mice, the expression pattern of human cyclin E faithfully reproduces that normally associated with mouse cyclin D1. The replacement of cyclin D1 with cyclin E rescues all phenotypic manifestations of cyclin D1 deficiency and restores normal development in cyclin D1-dependent tissues. Thus, cyclin E can functionally replace cyclin D1. Our analyses suggest that cyclin E is the major downstream target of cyclin D1.
D型细胞周期蛋白和细胞周期蛋白E代表了两类截然不同的哺乳动物G1期细胞周期蛋白。我们构建了一种小鼠品系，其中细胞周期蛋白D1基因（Ccnd1）的编码序列已被删除，并被人细胞周期蛋白E（CCNE）的编码序列所取代。在这些小鼠的组织和细胞中，人细胞周期蛋白E的表达模式忠实地再现了通常与小鼠细胞周期蛋白D1相关的表达模式。用细胞周期蛋白E替代细胞周期蛋白D1挽救了细胞周期蛋白D1缺陷的所有表型表现，并恢复了细胞周期蛋白D1依赖性组织的正常发育。因此，细胞周期蛋白E在功能上可以替代细胞周期蛋白D1。我们的分析表明，细胞周期蛋白E是细胞周期蛋白D1的主要下游靶点。
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